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Updated: Jan 16, 2026

Unilateral Ureteral Obstruction Model for Investigating Kidney Interstitial Fibrosis
Published on: April 25, 2025
Apoptosis Inhibitor of Macrophage (AIM) Modulates Calcium Oxalate-Induced Ureteral Fibrosis in AIM-Felinized Mice
Yuka Machida1, Masaki Watanabe2, Fumi Suzuki1
1Laboratory of Small Animal Surgery 2, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan.
Abstract:
Calcium oxalate (CaOx) stones account for 90% of uroliths in cats and contribute to ureteral inflammation and fibrosis, although the underlying mechanism remains unclear. Apoptosis inhibitor of macrophage (AIM) is known to play a protective role against tubular injury in feline kidney disease. This study investigated whether AIM contributes to ureteral fibrosis by using AIM-felinized mice subjected to CaOx bead-induced ureteral injury. Male C57BL/6 mice (n = 54), including wild-type mice (mA), AIM-knockout (koA) mice, and AIM-felinized mice (fA), were assigned to either a unilateral ureteral obstruction (UUO; U) group or a UUO plus CaOx implantation (C) group. Ureters were collected 14 days after the procedure for histopathological analysis. The severity of ureteral injury followed the order of koA-C ≥ fA-C > mA-C, indicating AIM's involvement in the injury process. Furthermore, fA exhibited more severe fibrosis than mA mice (p < 0.05), suggesting that mouse AIM may have stronger anti-fibrotic effects than feline AIM. These results suggest that AIM-felinized mice could serve as a useful model for investigating feline-specific ureteral pathology. To our knowledge, this is the first experimental study to explore the role of feline AIM in ureteral injury and fibrosis. Further studies are warranted to validate the utility of this model.
Insights
Apoptosis inhibitor of macrophage (AIM) plays a role in feline ureteral fibrosis caused by calcium oxalate (CaOx) stones. AIM-felinized mice offer a model for studying this condition.
Area of Science:
- Nephrology
- Urology
- Pathology
Background:
- Calcium oxalate (CaOx) stones are the primary cause of feline uroliths, leading to ureteral inflammation and fibrosis.
- The precise mechanisms underlying CaOx-induced ureteral damage are not fully understood.
- Apoptosis inhibitor of macrophage (AIM) has demonstrated protective effects against kidney injury in felines.
Purpose of the Study:
- To investigate the role of AIM in the development of ureteral fibrosis following CaOx stone injury.
- To evaluate the utility of AIM-felinized mice as a model for feline ureteral pathology.
Main Methods:
- Male C57BL/6 mice, including wild-type, AIM-knockout, and AIM-felinized strains, were subjected to unilateral ureteral obstruction (UUO) with or without CaOx bead implantation.
- Ureters were collected after 14 days for histopathological analysis to assess injury and fibrosis.
- Comparative analysis was performed between different mouse strains and experimental groups.
Main Results:
- Ureteral injury severity correlated with AIM status, with AIM-knockout mice showing the most severe damage.
- AIM-felinized mice exhibited more severe ureteral fibrosis than wild-type mice, suggesting mouse AIM has stronger anti-fibrotic properties.
- The findings indicate AIM's involvement in the ureteral injury and fibrosis process.
Conclusions:
- AIM-felinized mice represent a valuable experimental model for studying feline-specific ureteral pathology.
- This study provides initial evidence for the role of feline AIM in ureteral injury and fibrosis.
- Further research is needed to confirm the efficacy of this model in preclinical studies.

